COMPOSITIONS AND METHODS FOR BLOOD-BRAIN BARRIER DELIVERY OF lgG-DECOY RECEPTOR FUSION PROTEINS
AssigneeArmaGen Technologies, Inc.
InventorsWilliam M. Pardridge, Ruben J. Boado
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Abstract
Provided herein are compositions and related methods for delivering an IgG-decoy receptor to the CNS. The methods include systemic administration of a bifunctional decoy receptor-BBB receptor antibody fusion antibody comprising a receptor extracellular domain (ECD) covalently linked to an antibody to a receptor expressed on the surface of the blood-brain barrier (BBB receptor). In some embodiments, the compositions described herein are administered to treat a subject suffering from a CNS condition.
Claims55
A bifunctional decoy receptor fusion antibody comprising the amino acid sequence of a heavy chain immunoglobulin or a light chain immunoglobulin covalently linked to the amino acid sequence of a receptor extracellular domain, wherein the fusion antibody binds to a receptor expressed on the BBB and a ligand for the receptor extracellular domain.
A nucleic acid comprising:
- (i) a first sequence encoding a heavy chain immunoglobulin and a receptor extracellular domain in frame with the heavy chain immunoglobulin;
- (ii) a second sequence encoding a light chain immunoglobulin and a receptor extracellular domain in frame with the light chain immunoglobulin;
- or
- (iii) the complementary sequence of (i) or (ii);
- wherein
- the heavy chain and light chain immunoglobulin are from an antibody against a BBB receptor.
A method for delivering a decoy receptor across the blood brain barrier, comprising systemically administering to a subject a pharmaceutical composition comprising a bifunctional decoy receptor fusion antibody comprising the amino acid sequence of a heavy chain immunoglobulin or a light chain immunoglobulin covalently linked to the amino acid sequence of a receptor extracellular domain, wherein the fusion antibody binds to a receptor expressed on the BBB and the ligand for the receptor extracellular domain.
A method for treating a CNS condition, comprising systemically administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a bifunctional decoy receptor fusion antibody comprising the amino acid sequence of a heavy chain immunoglobulin or a light chain immunoglobulin covalently linked to the amino acid sequence of a receptor extracellular domain, wherein the fusion antibody binds to a receptor expressed on the BBB and the ligand for the receptor extracellular domain.
A method for manufacturing a bifunctional decoy receptor fusion antibody, comprising stably integrating into a eukaryotic cell a single tandem expression vector encoding:
- (i) both an immunoglobulin heavy chain fused to a receptor extracellular domain, and an immunoglobulin light chain;
- or
- (ii), both an immunoglobulin light chain fused to a receptor extracellular domain, and an immunoglobulin heavy chain, wherein the encoded immunoglobulin heavy chain and immunoglobulin light chain are from an antibody against a receptor expressed on the BBB.
Dependencies are inferred from the claim text.